Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study.

Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study. Mei Yang, Lin Li, Chunfan Jiang, Xiaomin Qin, Min Zhou, Xiaogang Mao, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-22259/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Sep, 2020 Read the published version in BMC Infectious Diseases → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background: Evidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). Methods: From January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions. Results: Among 310,545 female, 6,067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p<0.0001). Co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 (OR 1.71, 95% CI: 1.16-2.53). Conclusions: Co-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions. Infectious Diseases Invasive Cervical Cancer Cervical Intraepithelial Neoplasia Human Papillomavirus Vaginal Microenvironment Trichomonas Vaginitis Figures Figure 1 Figure 2 Figure 3 Background Cervical cancer is a common malignant tumor of the female reproductive system, and it progresses rapidly with a high mortality rate [1] . HPV is a DNA virus, which is widely found in nature. Hr-HPV (e.g. HPV 16, 18, 31, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) among them are associated with high grade cervical intraepithelial neoplasia and invasive cervical cancer. Under normal conditions, vaginal flora is composed of more than 20 kinds of microbes [2, 3] . Infection of the female reproductive tract refers to a series of infectious inflammation caused by the destruction of the defense system by microorganisms, such as viruses and bacteria [4] . The genital tract infection leads to an imbalance of the vaginal flora, which inhibits or reduces the lactobacillus substantially, which may cause the decline of the clearance of hr- HPV. Candida spp, Gardnerella and TV are the most common vaginal infections. As a part of the human commensal flora, Candida spp always causes systemic and superficial infections [5] . Gardnerella vaginalis is considered as playing a vital role in the pathogenesis of bacterial vaginitis (BV) [6] , and BV shows a correlation with severity of cervical neoplasia in HPV-positive female [7] . Still the aetiology and pathogenesis of BV are more complex, Gardnerella vaginalis is thought as a potential founder organism. As a sexually transmitted infectious agent, TV is found to cause local inflammation, and it affects the clearance of hr-HPV and contributes to cervical lesion detection in several research, but it is controversial [8] . Some studies have demonstrated a correlation between vaginal infection and the carcinogenicity of hr-HPV, but most of them are small-scale researches, and their conclusions are inconsistent [5, 9-16] . This research is with the most massive scale and the most comprehensive investigation about the correlation between cervical hr-HPV infection, CIN/ICC, and the vaginal microbiome. Central China is one of the regions with the highest incidence of cervical cancer [17] , and the social-economic conditions vary significantly in different districts. To study ICC influenced by multiple socioeconomic factors, nine areas in Central China with significantly different economic levels were included in this study. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of hr-HPV. Methods This project had been conducted in Central China from January 15, 2017 to December 31, 2017. Female aged at least 30 years old were recruited to undergo cervical cancer screening from 9 clinical research centers (Xiangzhou, Fancheng, Xiangcheng, Baokang, Nanzhang, Zaoyang, Yicheng, Gucheng and Laohekou) in Central China via media promotion and government notices. Female who received hysterectomy, were pregnant, without sexual history had been excluded. All the female had not been vaccinated against cervical cancer yet. All the participants received questionnaires, hr-HPV genotyping, and vaginal microbiota examination. The screening process was based on the interim clinical guidance of ASCCP in 2015 [18] , female tested positive for HPV 16 and HPV 18 had been referred to colposcopy directly; female with other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly. The protocol was approved by the Ethics Committee of Xiangyang Central Hospital. 2.1 Questionnaires All the recruited participants were interviewed by a trained interviewer and filled out a questionnaire (Additional file 1) for the first time. The content of the questionnaire includes age, marital status, ethnicity, the highest level of education, whether in menopause, date of last menstruation, history of past HPV infection, family history of cancer, reproductive history (number of pregnancies and number of births), method of contraception (contraceptive, condom and intrauterine contraceptive device), number of lifetime sex partners and whether in poverty (whether being a poverty alleviation target). 2.2 HPV genotyping All the recruited female underwent a gynecological examination. A cervical specimen was taken using a cervical brush, and a high vaginal swab was collected. COBAS4800 (Roche Molecular Systems, Alameda, CA) assay was used for typing HPV DNA. The COBAS 4800 HPV test detected a total of 14 hr-HPV types simultaneously: HPV-16 individually, HPV-18 individually, and pooled hr-HPV genotypes other than HPV 16 and 18 (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68), in addition to a separate high b-globin control. 2.3 Vaginal microenvironment test The high vaginal swab was processed for microscopic evaluation of vaginal microenvironment, including the presence of Candida albicans, TV, Gardnerella, clue cells, and miscellaneous bacteria (vaginal bacteria except for lactobacilli) density [19] . A vaginal wet mount was prepared for the detection of Candida albicans. Candida was diagnosed using the KOH method (10% KOH), and vaginal trichomonas was examined according to conventional methods, the swimming trichomonas was observed under the microscope (x400). Gardnerella, clue cells, and miscellaneous bacteria density(MBD) were observed by Gram staining. The scoring method of miscellaneous bacteria density was listed as follows, and no miscellaneous bacteria was scored as Ⅰ, 1–5 miscellaneous bacteria/OML as Ⅱ, 6–30 miscellaneous bacteria/OML as Ⅲ, ＞30 miscellaneous bacteria/OML as Ⅳ [19] . 2.4 Thinprep cytologic test According to the manufacturer’s instructions, slides for liquid-based cytology were prepared. Bethesda System 2001 terminology was used for reporting the results [20] . The following five different categories were reported: negative for intraepithelial lesion or malignancy (NILM); atypical glandular cells (AGC); squamous intraepithelial lesion (SIL): low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL); atypical squamous cells of undetermined significance (ASC-US) or atypical squamous cells not possible exclude HSIL (ASC-H) and squamous cell carcinoma (SCC). 2.5 Colposcopy-directed biopsy and verification of disease status Female with positive HPV 16 and HPV 18 through the test or with other hr-HPV types through the test and the result of liquid-based cytology ≥ ASCUS underwent further cervical biopsy and/or endocervical curettage (ECC) by a local trained gynecologist in each hospital. The cervical tissues underwent the preparation of histological sections. Two pathologists made the diagnosis separately. The histological diagnoses of cervical lesions were divided into normal, CIN1, CIN2, CIN3 and ICC according to the WHO criteria for the pathological staging of cervical lesions [21, 22] . CIN1(cervical intraepithelial neoplasia grade 1): cells showed light atypia and irregular arrangement, but remained polar, and the abnormal proliferated cells were limited to the subcortical 1/3. CIN2(cervical intraepithelial neoplasia grade 2): cells showed obvious atypia and disordered arrangement. Abnormal proliferated cells occupied 2/3 of the subcortical area. CIN3(cervical intraepithelial neoplasia grade 3): Severe atypical hyperplasia of the epithelial cells were significantly atypia, loss of polarity, abnormal proliferation of cells expanded to 2/3 of the epithelium or almost the entire layer, difficult to distinguish from carcinoma in situ.The epithelial atypia cells of carcinoma in situ involved the whole layer, with no polarity, significant nuclear atypia and more mitotic phases.The basement membrane of the epithelium was intact without stroma infiltration. ICC(invasive cervical cancer): Cancer cells break through the basement membrane. (I suggest describing in more detail the method used for pathological staging or including the reference that supports it.) 2.6 Statistical analysis Histological results (normal, CIN1, CIN2, CIN3 and ICC) were distributed among respective hr-HPV types and then evaluated. Univariate analysis was used for comparing whether the risk of any cervical lesions (tri categorical: CIN1, CIN2-3 and ICC) differed when female having a vaginal infection (Candida albicans, Gardnerella and TV) or not. Odds ratios and 95% confidence intervals (CIs) were calculated to study the specific risk among different HPV types. Next, social-demographic and reproductive characteristics were taken into consideration so as to improve the accuracy of the results. These characteristics of the participants were presented as proportions. Correlations between specific vaginal infection and hr-HPV genotype and CIN/ICC were assessed using stepwise logistic regression after adjusting for all potential risk factors. ORs and 95% CIs were calculated to analyze the correlation between possible risk factors and pathogenic infection. Data was analyzed with SPSS Software Version 20.0. Results 3.1 The overall prevalence of hr-HPV, Candida albicans, Gardnerella and TV Among 310,545 participants, 24,364 (7.84%) female were infected with hr-HPV. Candida albicans were detected in 13,763 (4.43%) female, Gardnerella were detected in 1,050 (0.34%) female, and TV were tested positive in 5,683 (1.83%) female, respectively. 3.2 Distribution of HPV types in CIN and ICC female from Central China 307,071 female received complete screening process finally (1,331 female with HPV 16 and HPV 18 and 1,241 female with other positive hr-HPV were failed to follow up for different reasons, such as changes of the workplace, health problems or other personal reasons, 902 samples failed to prepare slides for liquid-based cytology for having too little cells.) 6,067(1.95%) female were tested positive for HPV 16 and HPV 18, including HPV 16 only, HPV 16+ other high risk (OHR), HPV 18 only, HPV 18+ OHR, HPV 16+18, and HPV 16+ 18+ OHR types. 4,736 (1.53%) among them, received colposcopy, CIN1, CIN2, CIN3, ICC were detected in 480 (0.15%) cases, 265 (0.086%) cases, 346 (0.11%) cases, 75 (0.024%) cases, respectively. 18,297 (5.89%) female were tested positive only for other hr-HPV genotypes, and undertook triage using liquid-based cytology. 2,350 (0.76%) cases with the results ≥ ASCUS were referred to colposcopy directly, and CIN1, CIN2, CIN3 and ICC were detected in 381 (0.12%) cases, 112 (0.036%) cases, 77 (0.025%) cases, 2 cases, respectively (Figure 1). 3.3 Correlation between Candida Albicans, Gardnerella, TV and the detection of cervical lesions stratified by different hr-HPV types The distribution of potential risk factors among CIN/ICC and normal participants are shown in Additional file 2. Univariate analysis of the correlation between different vaginal infection (Candida albicans, Gardnerella, TV micro-environment) and the histological results (three categories: CIN1, CIN2-3 and ICC) among different hr-HPV types is displayed in Figure 2 and Additional file 3. In HPV 16 infection groups, when co-infected with TV, female had a significantly higher incidence of CIN 1 (OR = 1.301, 95% CI = 1.003-1.685), CIN 2-3 (OR = 2.066, 95% CI = 1.625-2.627) and ICC (OR = 2.546, 95% CI = 1.248-5.191). In HPV 18 positive groups, the co-infection of TV didn’t increase the risk of CIN1, CIN2-3, or ICC. In all the different hr-HPV types, no significant correlation was found between Candida albicans, Gardnerella co-infection, and any cervical lesions. 3.4 Multivariate analysis of the risk of CIN/ICC by TV stratified by hr-HPV infection status Among the overall participants, 5,683 (1.83%) participants were infected with TV; among them, 1,952 (0.63%) female were co-infected with hr-HPV. Among the co-infection population, 1,643 cases had normal cytology or histologic diagnosis, 171 cases had CIN 1, 60 cases had CIN 2, 67 cases had CIN3 and 11 cases had ICC (Table 1). Multivariate logistic regression analyses were used for analyzing the risk of CIN 1, CIN 2-3 and ICC by TV stratified by different hr-HPV infection status. After adjusting the age, education, number of pregnancies, number of births, menopause, candida albicans, Gardnerella and miscellaneous bacteria density, method of contraception, lifetime sex partners and poverty, it was found that among total female infected with hr-HPV, TV increased the risk of CIN1 (OR 1.18, 95% CI: 1.42-2.31), but it did not increase the risk of CIN2-3 and ICC. For different HPV types, TV increased the risk of CIN2-3 among the female infected with HPV16 (single HPV16 or simultaneous infection of HPV 16 and other high-risk HPV types) (OR 1.71, 95% CI: 1.16-2.53). For there were only 77 ICC female in this study, no efficient results were found among HPV 16 positive ICC female. No positive correlation were found between TV and CIN 1/CIN 2-3/ICC among none HPV16 positive female in this study (Table 2). 3.5 Potential Risk Factors of hr-HPV mono-infection or co-infection with TV To find the risk factors of hr-HPV infection, multivariate logistic regression analyses were utilized. The results are shown in Figure 3; it was found that age ≥ 60 (p<0.001), number of pregnancies ≥ 1 (p<0.001), postmenopause (p<0.01), poverty (p<0.01), personal HPV history (p<0.01), miscellaneous bacteria density (p<0.0001), trichomonas (p<0.0001), were positively associated with hr-HPV infection significantly; Education(p=0.0154), was not associated with hr-HPV infection; Number of birth, and candida infection were negatively correlated with hr-HPV infection (p<0.0001). Baseline features of the participants with hr-HPV and TV co-infection are shown in Table 3, primary education, intrauterine contraceptive device as a method of contraception and female with multiple sex partners were more likely to be infected with both TV and hr-HPV. Discussion Though it is recommended to begin primary hrHPV screening at age 25 years in the interim clinical guidance of ASCCP in 2015 [18] , it raises a number of concerns and questions. When compared to the same strategy starting at 30 years of age, starting at 25 years of age resulted in much higher detection of CIN3+. Still progression to cancer is uncommon, so It is unclear that the identification of these women with CIN3+ would translate into a meaningful reduction of cervical cancer [23] . Furthermore, the panel had concerns regarding the potential harms of beginning primary hrHPV screening at age 25 years, particularly with regard to the number of colposcopies, despite the increased detection of disease [24] . According to the report "Global Cancer Statistics 2018", cervical cancer ranks the fourth in the incidence and mortality of female tumors worldwide, and the second in the rate of female tumors in developing countries [1] . HPV infection is a necessary but insufficient condition for cervical cancer [25] ; the number of cervical cancer patients is far lower than the number of HPV infection female [26] . With the development of microbiome, more studies have shown that the composition and changes of the cervical-vaginal microenvironment are closely related to HPV invasion, persistent infection, and the occurrence and development of cervical cancer [27, 28] . In our study, the prevalence of hr-HPV in this region was lower than the hr-HPV prevalence from other parts of China (from 9.03% to 16.8%) [17] . The cervical cancer vaccine had not been introduced in China at the time of screening, so all the female had not been vaccinated against HPV yet. This is the first time we have relatively accurate data on hr-HPV infection rates in central China. It was found that Candida spp was not associated with the detection of cervical lesions in this study, consistent with previous studies [5, 13, 14] . Gardnerella vaginalis was not the risk factor of CIN or ICC in our research, either. Gardnerella vaginalis was considered to possess characteristics which are essential for the pathogenesis of BV [6, 29-31] , including the production of sialidase [31] and vaginolysin, [30, 32] . Although some research found that BV played a functional role in female with CIN or ICC [2, 3] , the correlation between Gardnerella and the progression of cervical lesions had yet to be described. In this study, Gardnerella has had a low prevalence and was only detected in 1,050 (0.34%) female, and co-infected with Gardnerella didn’t increase the risk of CIN or ICC. In the vagina of female without BV, Gardnerella vaginalis was also detected, although it had a lower abundance and prevalence [33, 34] . There was enormous substantial genetic diversity within Gardnerella vaginalis [16, 35] , and virulence potential differentiate significantly between various genetic types/clades [15] ; this may correlate with the result in our study. Several pieces of research had concerned the relationship between TV, HPV and CIN/ICC, but their conclusions were inconsistent. Gweneth’s study found that trichomonas vaginitis was associated with hr-HPV infection (specifically type 16) significantly, but no correlation between trichomonas and cervical lesions [10] . Ishita Ghosh’s study found that the higher risk of cervical cancer observed in the female co-infected with HPV and TV was without any enhanced risk of CIN [5] . But both of them were small-scale studies. Rui-Mei Feng’s pooled analysis found that current TV-positive female had an increased risk for hr-HPV infection compared with currently TV negative female. Both past and current TV-positive female had a decreased risk for CIN 2+ [9] , but hr-HPV was detected by Hybrid Capture 2 and HPV genotype can’t be differentiated, TV was diagnosed by thinprep cytologic test in that research, and this method had a lower detection rate. In this study, 5,683 among the overall participants were TV positive and 1,952 (34.35%) among these, were co-infected with hr-HPV. Co-infection with TV increased the risk of CIN 1 among female with hr-HPV, and increased the risk of CIN 2-3 among female with HPV 16. It was expected that TV was often associated with more severe inflammatory reaction and HPV persistence, and was likely closely related to the invasion, persistent infection of HPV 16. HPV including hr-HPV infections are mostly temporary. The virus can be cleared through host immune responses spontaneously, only a small number of infections persisted and progressed to cervical cancer [36] . HPV 16 was found to be the most prevalent hr-HPV type with the highest risk among all hr-HPVs to progress to CIN2-3 and ICC [37] . Studies found that the outcome of HPV infection was closely related to the local micro-environmental of the cervix [27] . A lot of research has discovered that TV led to an imbalance of the vaginal flora, which inhibited or reduced the lactobacillus substantially [5] , and caused severe inflammation. Evidence were found that the continuous activation of inflammatory transcription factors can lead to cervical tissue damage, and thus improved the susceptibility and carcinogenic ability of HPVl6 [10, 38] . Meanwhile, the severity of cervical lesions was correlated with the abundance and diversity of cervicovaginal flora positively and correlated with the number of lactobacilli negatively [27, 39] . Unlike CIN 1, CIN 2-3 had been considered no longer reversible and required a more definite clinical treatment, the composition and characteristics of the cervical and vaginal flora were very different [40] . [2, 3] . There may be some complex host immune response to TV and HPV 16 co-infection, but the hypothesis needed further research for validation. There were only 72 ICC in this study, so the correlation between TV, HPV and ICC were inconclusive. Both TV and genital tract HPV infection are sexually transmitted disease (STD). In the districts with lower economic levels, many people went out to the developed areas to work and couples usually work in different places, and sex act extramarital is common [17] . Risk factors including primary education, intrauterine contraceptive device as a method of contraception and female with multiple sex partners significantly increased the odds of hr-HPV and TV co-infection. Compared with female with only one sexual partner, it was found that female with two or more lifetime sex partners had a higher risk of HPV and TV co-infection. Meanwhile, it was found that female who chose intrauterine contraceptive device as a method of contraception had a higher risk of co-infection, as compared with female who chose contraceptive or condom. Female who had primary education also were found to have a higher risk of co-infection compared with higher educated female. As TV is a STD, and it was found that two or more lifetime sex partners and choosing intrauterine contraceptive device instead of condom were associated with co-infection, it was expected that the co-infection is likely closely related to the risky sex behaviors. Sexual interactions with multiple hosts were expected to contribute to the co-infection, because each host may be infected with one kind of special pathogen species [41, 42] . The transmission and clinical progression of sexually transmitted infectious diseases may be changed by sexual interactions [43, 44] . Risk factors, including the number of pregnancies ≥ 1, post-menopause, poverty, personal HPV history and miscellaneous bacteria density were associated with HPV infection significantly, but they were not related to co-infection significantly. As it was known that, this research had the largest number of female who received COBAS human papillomavirus primary testing for cervical cancer screening up to now worldwide, and it was a multisite investigation with the most massive scale about the correlation between cervical hr-HPV infection, CIN/ICC and vaginal microenvironment. The detection methods of hr-HPV and vaginal microenvironment in this study were highly sensitive and recognized internationally. Of note, there were some limitations to our study. Because our study was a cross-sectional analysis of current hr-HPV and TV infections, one of its major limitations, which is inherent to the design, is that the association found does not imply causality. It was not clear whether there was a persistent infection among these female or not, so follow-up of TV-infected women to assess whether new CIN detection or CIN stage progression occurs would result in a much more clarifying study to support our findings. Besides, there are some participants who failed to be followed up for a variety of reasons in the screening process. chlamydia has been detected less and less, so it was not included in this study. HIV-infection status and smoking habit has not been included in this study. Conclusions From this large population-based study, it was found that Positive TV was correlated with hr-HPV infection and co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV, co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16. From what has been discussed above, co-infection of TV and HPV 16 is a significant risk factor for the detection of cervical lesions. For our study was a cross-sectional analysis, there were some limitations, and follow-up of TV-infected women to assess whether new CIN detection or CIN stage progression occurs will be the next step of our work. Declarations Ethics approval and consent to participate This study received the verification of Medicine Ethics Committee Xiangyang Central Hospital(Approved Code: 2017-004). The project “Biological Sample Bank Construction Project of Xiangyang City ‘Two Cancers Screening’” hosted by Xiangyang Central Hospital involves the collection of samples and related indicators detection of human cervical exfoliated cells and vaginal secretions. The related experiments of this project will strictly abide by ICH-GCP, declaration of Helsinki, International Ethical Guidelines for Biomedical Research Involving Human Subjects. Respect for the right of informed consent of the patient. All the experiments meet routine medical and make protection scheme for patients. All the members of Medicine Ethics Committee approved this project and gave a written consent. Informed consent to participate in this study had been obtained from participants. Consent to publish Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests All authors declare that they have no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. Funding This work was supported by the National Natural Science Foundation of China(No.81972449). Health Commission Foundation of Hubei, China (No. WJ2019M069); The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript. Authors' Contributions Designed project: XH, LL. Collected samples: QXM, ZM, MXG. Analyzed data: YM, JCF. Generated figures and tables: YM, JCF. Wrote manuscript: YM. All authors read and approved the final manuscript. Acknowledgments The authors thank the clinic staff of the hospitals which take part in the cervical cancer screening project in Central China in 2017. Legend Figure 1 Flowchart of screening profile. Among 310545 women, 6067 were tested positive for HPV 16/18, CIN1, CIN2, CIN3, ICC were detected in 480, 265, 346, 75 cases, respectively. 18297 were tested positive for other hr-HPV genotypes, CIN1, CIN2, CIN3, ICC were detected in 381, 112, 77, 2 cases, respectively. Figure 2 Univariate analyses of Candida albicans, Gardnerella, TV for the risk of CIN1/CIN2-3/ICC in different hr-HPV types. Figure 3 Multivariate analysis of hr-HPV infection. Age, highest level of education, number of pregnancies and number of births were set as rank variables. * MBD means miscellaneous bacteria density. Abbreviations abbreviations the full name hr-HPV high risk HPV CIN cervical intraepithelial neoplasia ICC invasive cervical cancer TV trichomonas vaginitis BV bacterial vaginitis MBD miscellaneous bacteria density NILM negative for intraepithelial lesion or malignancy AGC atypical glandular cells SIL squamous intraepithelial lesion LSIL low grade squamous intraepithelial lesion HSIL high grade squamous intraepithelial lesion ASC-US atypical squamous cells of undetermined significance ASC-H atypical squamous cells not possible exclude HSIL SCC squamous cell carcinoma ECC endocervical curettage CIs confidence intervals OHR other high risk STD sexually transmitted disease References [1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018. 68(6): 394-424. [2] Mitra A, MacIntyre DA, Lee YS, et al. 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Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007. 7(7): 453-9. [26] Monnier-Benoit S, Mauny F, Riethmuller D, et al. Immunohistochemical analysis of CD4+ and CD8+ T-cell subsets in high risk human papillomavirus-associated pre-malignant and malignant lesions of the uterine cervix. Gynecol Oncol. 2006. 102(1): 22-31. [27] Huang X, Li C, Li F, Zhao J, Wan X, Wang K. Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types. Int J Cancer. 2018. 143(3): 621-634. [28] Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next. Microbiome. 2016. 4(1): 58. [29] Schwebke JR, Muzny CA, Josey WE. Role of Gardnerella vaginalis in the pathogenesis of bacterial vaginosis: a conceptual model. J Infect Dis. 2014. 210(3): 338-43. [30] Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005. 106(5 Pt 1): 1013-23. [31] Lewis WG, Robinson LS, Gilbert NM, Perry JC, Lewis AL. Degradation, foraging, and depletion of mucus sialoglycans by the vagina-adapted Actinobacterium Gardnerella vaginalis. J Biol Chem. 2013. 288(17): 12067-79. [32] Gelber SE, Aguilar JL, Lewis KL, Ratner AJ. Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis. J Bacteriol. 2008. 190(11): 3896-903. [33] Schwebke JR, Flynn MS, Rivers CA. Prevalence of Gardnerella vaginalis among women with lactobacillus-predominant vaginal flora. Sex Transm Infect. 2014. 90(1): 61-3. [34] Yang L, Hao Y, Hu J, et al. Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women. Emerg Microbes Infect. 2019. 8(1): 197-210. [35] Hinderfeld AS, Phukan N, Bär AK, Roberton AM, Simoes-Barbosa A. Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions. Infect Immun. 2019. 87(5). [36] Borgdorff H, Gautam R, Armstrong SD, et al. Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier. Mucosal Immunol. 2016. 9(3): 621-33. [37] Vintermyr OK, Andersland MS, Bjørge T, Skar R, Iversen OE, Nygård M, et al. Human papillomavirus type specific risk of progression and remission during long-term follow-up of equivocal and low-grade HPV-positive cervical smears. Int J Cancer. 2018; 143:851-60. [38] Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis. 2014; 209:1989-99. [39] Zhang C, Liu Y, Gao W, et al. The direct and indirect association of cervical microbiota with the risk of cervical intraepithelial neoplasia. Cancer Med. 2018. 7(5): 2172-2179. [40] Łaniewski P, Barnes D, Goulder A, et al. Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women. Sci Rep. 2018. 8(1): 7593. [41] Ye X, Liu J, Yi Z. Trends in the Epidemiology of Sexually Transmitted Disease, Acquired Immune Deficiency Syndrome (AIDS), Gonorrhea, and Syphilis, in the 31 Provinces of Mainland China. Med Sci Monit. 2019. 25: 5657-5665. [42] Silverman RA, Katz DA, Levin C, et al. Sexually Transmitted Disease Partner Services Costs, Other Resources, and Strategies Across Jurisdictions to Address Unique Epidemic Characteristics and Increased Incidence. Sex Transm Dis. 2019. 46(8): 493-501. [43] Pedersen AB, Fenton A. Emphasizing the ecology in parasite community ecology. Trends Ecol Evol 2007;22:133-9, doi:http://dx.doi.org/10.1016/j.tree.2006.11.005. [44] Sternberg ED, Lefèvre T, Rawstern AH, de Roode JC. A virulent parasite can provide protection against a lethal parasitoid. Infect Genet Evol 2011;11:399-406, doi:http://dx.doi.org/10.1016/j.meegid.2010.11.017. Tables Table 1. Histologic diagnosis distribution in 1952 hr-HPV and TV co-infection population. HPV genotype Normal # n (%) * CIN1 n (%) CIN2 n (%) CIN3 n (%) Cancer n (%) Total n 16 Single-infection 1127(61.48) 234(12.77) 161(8.78) 260(14.18) 51(2.78) 1833 Co-infection 35(71.69) 68(13.85) 23(4.68) 42(8.55) 6(1.22) 491 16+OHR Single-infection 492(63.48) 121(15.61) 75 (9.68) 75 (9.68) 12(1.55) 775 Co-infection 132(69.84) 25(13.23) 15(7.94) 15(7.94) 2(1.06) 189 16+18 Single-infection 24(55.81) 10(23.26) 5(11.63) 4(9.3) 0(0) 43 Co-infection 5(45.45) 3(27.27) 1(9.09) 1(9.09) 1(9.09) 11 16+18+OHR Single-infection 30(63.83) 6(12.77) 9(19.15) 1(2.13) 1(2.13) 47 Co-infection 3(50) 1(16.67) 1(16.67) 1(16.67) 0(0) 6 18 Single-infection 401(77.12) 82(15.77) 16(3.08) 10(1.92) 11(2.12) 520 Co-infection 87(82.86) 13(12.38) 3(2.86) 1(0.95) 1(0.95) 105 18+OHR Single-infection 169(73.48) 51(22.17) 6(2.6) 4(1.74) 0(0) 230 Co-infection 15(46.87) 14(43.75) 2(6.25) 1(3.13) 0(0) 32 OHR Single-infection 16916(96.95) 357(2.05) 105(0.60) 69(0.39) 2(0.01) 17449 Co-infection 1049(93.83) 47(4.20) 15(1.34) 6(0.54) 1(0.09) 1118 #: female who have normal histologic or cytology results. OHR: other high risk type.( *percentages are calculated in turn; OHR-other high risk.) Table 2 Multivariate logistic regression analyses of the risk of CIN1/CIN2-3/ICC by TV stratified by hr-HPV infection status CIN1 CIN2-3 ICC n OR p n OR p n OR p Total 861 1.18(1.42-2.31) <.0001 800 1.17(0.88-1.55) 0.2735 77 0.99(0.36-2.75) 0.9898 16 371 0.69(0.48-1.01) 0.0501 590 1.71(1.16-2.53) 0.0069 64 - - 18 149 1.96(0.85-4.51) 0.112 55 2.18(0.75-6.34) 0.1544 12 - - OHR 535 0.73(0.49-1.08) 0.1147 344 0.90(0.56-1.45) 0.6704 15 0.36(0.12-1.06) 0.0633 Adjusted for age, the highest level of education, number of pregnancies, number of births, menopause, miscellaneous bacteria density, poverty, method of contraception, lifetime sex partners, gardnerella and candida spp. ( OHR-other high risk. ) Table 3 Baseline features of the participants with hr-HPV and TV co-infection OR(95%CI) P education <.0001 Primary ref Middle and high 0.424(0.377-0.476) Graduate 0.540(0.458-0.636) Marital status 0.1745 Married 0.729(0.462-1.150) Divorced or widowed ref Method of contraception <.0001 Non-contraception 0.236(0.207-0.270) Contraceptive 0.335(0.280-0.401) Condom 0.244(0.208-0.286) Intrauterine contraceptive device ref Lifetime sex partners <.0001 1 0.009(0.008-0.010) ≥2 ref Supplementary Files SupplementaryBMC813.doc Cite Share Download PDF Status: Published Journal Publication published 01 Sep, 2020 Read the published version in BMC Infectious Diseases → Version 3 posted Editorial decision: Accept 14 Aug, 2020 Editor assigned by journal 12 Aug, 2020 Submission checks completed at journal 11 Aug, 2020 Editor invited by journal 11 Aug, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-22259","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":1418905,"identity":"679c33f4-0a5f-4dda-9142-8c3ef3a50ec5","order_by":0,"name":"Mei Yang","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Yang","suffix":""},{"id":1418906,"identity":"88b3c47b-3b83-4141-b715-a09369073b5e","order_by":1,"name":"Lin Li","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lin","middleName":"","lastName":"Li","suffix":""},{"id":1418907,"identity":"f327caab-036e-43f9-901b-1e19c898c7d4","order_by":2,"name":"Chunfan Jiang","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chunfan","middleName":"","lastName":"Jiang","suffix":""},{"id":1418908,"identity":"e0903398-0a53-4f16-b38d-286d9d65af68","order_by":3,"name":"Xiaomin Qin","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaomin","middleName":"","lastName":"Qin","suffix":""},{"id":1418909,"identity":"61a477e0-c7dc-4141-abe3-d18aab05c523","order_by":4,"name":"Min Zhou","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Zhou","suffix":""},{"id":1418910,"identity":"a8c142a1-ada7-4a65-9061-89e28bc6f5d5","order_by":5,"name":"Xiaogang Mao","email":"","orcid":"","institution":"Xiangyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaogang","middleName":"","lastName":"Mao","suffix":""},{"id":1418911,"identity":"084f15e3-32df-47f9-ac8f-3760bdfb65fc","order_by":6,"name":"Hui Xing","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBAC+2bmgw8+VBxIgHDZiNBiwN6WbDjjDElaeM6YCfO2kaLFXCLBjJl33p08g+PHHzB8KDvMwD+7Ab8WyxkJaQ/nbntWbHAmx4BxxrnDDBJ3DhCw5kbCcYO32w4nbjiQw8DM23aYwUAigZCWxDYJ3jlALeefP2D+S4wWgzOH2SR5G4BabiQYMDMSo0WyvY3ZcMaxw8WSN94YHOw5l84jcYOAFn5m/o8PPtQczuM7n/7wwY8yazn+GYT8ggwOADEPCepHwSgYBaNgFOACAB7HTpOZTeWSAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-0318-1735","institution":"Xiangyang Central Hospital","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Xing","suffix":""}],"badges":[],"createdAt":"2020-04-09 12:04:09","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.3.rs-22259/v3","doiUrl":"https://doi.org/10.21203/rs.3.rs-22259/v3","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-020-05349-0","type":"published","date":"2020-09-01T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1953707,"identity":"0245bdbb-d18d-41cf-97ec-bb29a53e3616","added_by":"auto","created_at":"2020-08-17 14:25:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":261678,"visible":true,"origin":"","legend":"Flowchart of screening profile. Among 310545 women, 6067 were tested positive for HPV 16/18, CIN1, CIN2, CIN3, ICC were detected in 480, 265, 346, 75 cases, respectively. 18297 were tested positive for other hr-HPV genotypes, CIN1, CIN2, CIN3, ICC were detected in 381, 112, 77, 2 cases, respectively.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-22259/v3/1.jpg"},{"id":1953708,"identity":"64bce8cb-9926-4cd9-af8e-12d51ed6ee76","added_by":"auto","created_at":"2020-08-17 14:25:47","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":96057,"visible":true,"origin":"","legend":"Univariate analyses of Candida albicans, Gardnerella, TV for the risk of CIN1/CIN2-3/ICC in different hr-HPV types. ","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-22259/v3/2.jpg"},{"id":1953709,"identity":"6eed86f5-06be-404b-bbcd-3584d57da787","added_by":"auto","created_at":"2020-08-17 14:25:47","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":44115,"visible":true,"origin":"","legend":"Multivariate analysis of hr-HPV infection. Age, highest level of education, number of pregnancies and number of births were set as rank variables. * MBD means miscellaneous bacteria density.","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-22259/v3/3.jpg"},{"id":13576537,"identity":"36ff84e7-3573-4acf-8953-de8029bf1e69","added_by":"auto","created_at":"2021-09-17 04:08:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":590602,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-22259/v3/f31d38ea-8f1f-46b4-bfb2-3daeae3db7f6.pdf"},{"id":1953711,"identity":"1e7f0f9f-29af-4d97-8480-4a8c88401a4c","added_by":"auto","created_at":"2020-08-17 14:25:47","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":101376,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryBMC813.doc","url":"https://assets-eu.researchsquare.com/files/rs-22259/v3/SupplementaryBMC813.doc"}],"financialInterests":"","formattedTitle":"\u003cp\u003eCo-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study.\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eCervical cancer is a common malignant tumor of the female reproductive system, and it progresses rapidly with a high mortality rate \u003csup\u003e[1]\u003c/sup\u003e. HPV is a DNA virus, which is widely found in nature. Hr-HPV (e.g. HPV 16, 18, 31, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82) among them are associated with high grade cervical intraepithelial neoplasia and invasive cervical cancer.\u003c/p\u003e\n\u003cp\u003eUnder normal conditions, vaginal flora is composed of more than 20 kinds of microbes \u003csup\u003e[2, 3]\u003c/sup\u003e. Infection of the female reproductive tract refers to a series of infectious inflammation caused by the destruction of the defense system by microorganisms, such as viruses and bacteria \u003csup\u003e[4]\u003c/sup\u003e. The genital tract infection leads to an imbalance of the vaginal flora, which inhibits or reduces the lactobacillus substantially, which may cause the decline of the clearance of hr- HPV. Candida spp, Gardnerella and TV are the most common vaginal infections. As a part of the human commensal flora, Candida spp always causes systemic and superficial infections \u003csup\u003e[5]\u003c/sup\u003e. Gardnerella vaginalis is considered as playing a vital role in the pathogenesis of bacterial vaginitis (BV) \u003csup\u003e[6]\u003c/sup\u003e, and BV shows a correlation with severity of cervical neoplasia in HPV-positive female \u003csup\u003e[7]\u003c/sup\u003e. Still the aetiology and pathogenesis of BV are more complex, Gardnerella vaginalis is thought as a potential founder organism. As a sexually transmitted infectious agent, TV is found to cause local inflammation, and it affects the clearance of hr-HPV and contributes to cervical lesion detection in several research, but it is controversial \u003csup\u003e[8]\u003c/sup\u003e. Some studies have demonstrated a correlation between vaginal infection and the carcinogenicity of hr-HPV, but most of them are small-scale researches, and their conclusions are inconsistent \u003csup\u003e[5, 9-16]\u003c/sup\u003e. This research is with the most massive scale and the most comprehensive investigation about the correlation between cervical hr-HPV infection, CIN/ICC, and the vaginal microbiome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCentral China is one of the regions with the highest incidence of cervical cancer\u003csup\u003e[17]\u003c/sup\u003e, and the social-economic conditions vary significantly in different districts. To study ICC influenced by multiple socioeconomic factors, nine areas in Central China with significantly different economic levels were included in this study. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of hr-HPV.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis project had been conducted in Central China from January 15, 2017 to December 31, 2017. Female aged at least 30 years old were recruited to undergo cervical cancer screening from 9 clinical research centers (Xiangzhou, Fancheng, Xiangcheng, Baokang, Nanzhang, Zaoyang, Yicheng, Gucheng and Laohekou) in Central China via media promotion and government notices. Female who received hysterectomy, were pregnant, without sexual history had been excluded. All the female had not been vaccinated against cervical cancer yet. All the participants received questionnaires, hr-HPV genotyping, and vaginal microbiota examination. The screening process was based on the interim clinical guidance of ASCCP in 2015\u003csup\u003e[18]\u003c/sup\u003e, female tested positive for HPV 16 and HPV 18 had been referred to colposcopy directly; female with other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results \u0026ge; ASCUS among them were referred to colposcopy directly. The protocol was approved by the Ethics Committee of Xiangyang Central Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1 Questionnaires\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the recruited participants were interviewed by a trained interviewer and filled out a questionnaire (Additional file 1) for the first time. The content of the questionnaire includes age, marital status, ethnicity, the highest level of education, whether in menopause, date of last menstruation, history of past HPV infection, family history of cancer, reproductive history (number of pregnancies and number of births), method of contraception (contraceptive, condom and intrauterine contraceptive device), number of lifetime sex partners and whether in poverty (whether being a poverty alleviation target).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u003c/strong\u003e\u003cstrong\u003eHPV genotyping\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the recruited female underwent a gynecological examination. A cervical specimen was taken using a cervical brush, and a high vaginal swab was collected. COBAS4800 (Roche Molecular Systems, Alameda, CA) assay was used for typing HPV DNA. The COBAS 4800 HPV test detected a total of 14 hr-HPV types simultaneously: HPV-16 individually, HPV-18 individually, and pooled hr-HPV genotypes other than HPV 16 and 18 (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68), in addition to a separate high b-globin control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3 Vaginal microenvironment test\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe high vaginal swab was processed for microscopic evaluation of vaginal microenvironment, including the presence of Candida albicans, TV, Gardnerella, clue cells, and miscellaneous bacteria (vaginal bacteria except for lactobacilli) density\u003csup\u003e[19]\u003c/sup\u003e. A vaginal wet mount was prepared for the detection of Candida albicans. Candida was diagnosed using the KOH method (10% KOH), and vaginal trichomonas was examined according to conventional methods, the swimming trichomonas was observed under the microscope (x400). Gardnerella, clue cells, and miscellaneous bacteria density(MBD) were observed by Gram staining. The scoring method of miscellaneous bacteria density was listed as follows, and no miscellaneous bacteria was scored as Ⅰ, 1\u0026ndash;5 miscellaneous bacteria/OML as Ⅱ, 6\u0026ndash;30 miscellaneous bacteria/OML as Ⅲ, ＞30 miscellaneous bacteria/OML as Ⅳ\u003csup\u003e[19]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4\u003c/strong\u003e\u003cstrong\u003eThinprep cytologic test\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to the manufacturer\u0026rsquo;s instructions, slides for liquid-based cytology were prepared. Bethesda System 2001 terminology was used for reporting the results \u003csup\u003e[20]\u003c/sup\u003e. The following five different categories were reported: negative for intraepithelial lesion or malignancy (NILM); atypical glandular cells (AGC); squamous intraepithelial lesion (SIL): low grade squamous intraepithelial lesion (LSIL) or high grade squamous intraepithelial lesion (HSIL); atypical squamous cells of undetermined significance (ASC-US) or atypical squamous cells not possible exclude HSIL (ASC-H) and squamous cell carcinoma (SCC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.5 Colposcopy-directed biopsy and verification of disease status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFemale with positive HPV 16 and HPV 18 through the test or with other hr-HPV types through the test and the result of liquid-based cytology \u0026ge; ASCUS underwent further cervical biopsy and/or endocervical curettage (ECC) by a local trained gynecologist in each hospital. The cervical tissues underwent the preparation of histological sections. Two pathologists made the diagnosis separately. The histological diagnoses of cervical lesions were divided into normal, CIN1, CIN2, CIN3 and ICC according to the WHO criteria for the pathological staging of cervical lesions\u003csup\u003e[21, 22]\u003c/sup\u003e. CIN1(cervical intraepithelial neoplasia grade 1): cells showed light atypia and irregular arrangement, but remained polar, and the abnormal proliferated cells were limited to the subcortical 1/3. CIN2(cervical intraepithelial neoplasia grade 2): cells showed obvious atypia and disordered arrangement. Abnormal proliferated cells occupied 2/3 of the subcortical area. CIN3(cervical intraepithelial neoplasia grade 3): Severe atypical hyperplasia of the epithelial cells were significantly atypia, loss of polarity, abnormal proliferation of cells expanded to 2/3 of the epithelium or almost the entire layer, difficult to distinguish from carcinoma in situ.The epithelial atypia cells of carcinoma in situ involved the whole layer, with no polarity, significant nuclear atypia and more mitotic phases.The basement membrane of the epithelium was intact without stroma infiltration. ICC(invasive cervical cancer):\u0026nbsp;Cancer cells break through the basement membrane. (I suggest describing in more detail the method used for pathological staging or including the reference that supports it.)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.6\u003c/strong\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistological results (normal, CIN1, CIN2, CIN3 and ICC) were distributed among respective hr-HPV types and then evaluated. Univariate analysis was used for comparing whether the risk of any cervical lesions (tri categorical: CIN1, CIN2-3 and ICC) differed when female having a vaginal infection (Candida albicans, Gardnerella and TV) or not. Odds ratios and 95% confidence intervals (CIs) were calculated to study the specific risk among different HPV types. Next, social-demographic and reproductive characteristics were taken into consideration so as to improve the accuracy of the results. These characteristics of the participants were presented as proportions. Correlations between specific vaginal infection and hr-HPV genotype and CIN/ICC were assessed using stepwise logistic regression after adjusting for all potential risk factors. ORs and 95% CIs were calculated to analyze the correlation between possible risk factors and pathogenic infection. Data was analyzed with SPSS Software Version 20.0.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 The overall prevalence of hr-HPV, Candida albicans, Gardnerella and TV \u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong 310,545 participants, 24,364 (7.84%) female were infected with hr-HPV. Candida albicans were detected\u003c/p\u003e\n\u003cp\u003ein 13,763 (4.43%) female, Gardnerella were detected in 1,050 (0.34%) female, and TV were tested positive in 5,683 (1.83%) female, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u003c/strong\u003e\u003cstrong\u003eDistribution of HPV types in CIN and ICC female from Central China\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e307,071 female received complete screening process finally (1,331 female with HPV 16 and HPV 18 and 1,241 female with other positive hr-HPV were failed to follow up for different reasons, such as changes of the workplace, health problems or other personal reasons, 902 samples failed to prepare slides for liquid-based cytology for having too little cells.) 6,067(1.95%) female were tested positive for HPV 16 and HPV 18, including HPV 16 only, HPV 16+ other high risk (OHR), HPV 18 only, HPV 18+ OHR, HPV 16+18, and HPV 16+ 18+ OHR types. 4,736 (1.53%) among them, received colposcopy, CIN1, CIN2, CIN3, ICC were detected in 480 (0.15%) cases, 265 (0.086%) cases, 346 (0.11%) cases, 75 (0.024%) cases, respectively. 18,297 (5.89%) female were tested positive only for other hr-HPV genotypes, and undertook triage using liquid-based cytology. 2,350 (0.76%) cases with the results \u0026ge; ASCUS were referred to colposcopy directly, and CIN1, CIN2, CIN3 and ICC were detected in 381 (0.12%) cases, 112 (0.036%) cases, 77 (0.025%) cases, 2 cases, respectively (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3 Correlation between Candida Albicans, Gardnerella, TV and the detection of cervical lesions stratified by different hr-HPV types\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe distribution of potential risk factors among CIN/ICC and normal participants are shown in Additional file 2. Univariate analysis of the correlation between different vaginal infection (Candida albicans, Gardnerella, TV micro-environment) and the histological results (three categories: CIN1, CIN2-3 and ICC) among different hr-HPV types is displayed in Figure 2 and Additional file 3. In HPV 16 infection groups, when co-infected with TV, female had a significantly higher incidence of CIN 1 (OR = 1.301, 95% CI = 1.003-1.685), CIN 2-3 (OR = 2.066, 95% CI = 1.625-2.627) and ICC (OR = 2.546, 95% CI = 1.248-5.191). In HPV 18 positive groups, the co-infection of TV didn\u0026rsquo;t increase the risk of CIN1, CIN2-3, or ICC. In all the different hr-HPV types, no significant correlation was found between Candida albicans, Gardnerella co-infection, and any cervical lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4\u003c/strong\u003e\u003cstrong\u003eMultivariate analysis of the risk of CIN/ICC by TV stratified by hr-HPV infection status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong the overall participants, 5,683 (1.83%) participants were infected with TV; among them, 1,952 (0.63%) female were co-infected with hr-HPV. Among the co-infection population, 1,643 cases had normal cytology or histologic diagnosis, 171 cases had CIN 1, 60 cases had CIN 2, 67 cases had CIN3 and 11 cases had ICC \u0026nbsp;(Table 1).\u003c/p\u003e\n\u003cp\u003eMultivariate logistic regression analyses were used for analyzing the risk of CIN 1, CIN 2-3 and ICC by TV stratified by different hr-HPV infection status. After adjusting the age, education, number of pregnancies, number of births, menopause, candida albicans, Gardnerella and miscellaneous bacteria density, method of contraception, lifetime sex partners and poverty, it was found that among total female infected with hr-HPV, TV increased the risk of CIN1 (OR 1.18, 95% CI: 1.42-2.31), but it did not increase the risk of CIN2-3 and ICC. For different HPV types, TV increased the risk of CIN2-3 among the female infected with HPV16 (single HPV16 or simultaneous infection of HPV 16 and other high-risk HPV types) (OR 1.71, 95% CI: 1.16-2.53). For there were only 77 ICC female in this study, no efficient results were found among HPV 16 positive ICC female. No positive correlation were found between TV and CIN 1/CIN 2-3/ICC among none HPV16 positive female in this study (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.5 \u003c/strong\u003e\u003cstrong\u003ePotential Risk Factors of hr-HPV mono-infection or co-infection with TV\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo find the risk factors of hr-HPV infection, multivariate logistic regression analyses were utilized. The results are shown in Figure 3; it was found that age \u0026ge; 60 (p\u0026lt;0.001), number of pregnancies \u0026ge; 1 (p\u0026lt;0.001), postmenopause (p\u0026lt;0.01), poverty (p\u0026lt;0.01), personal HPV history (p\u0026lt;0.01), miscellaneous bacteria density (p\u0026lt;0.0001), trichomonas (p\u0026lt;0.0001), were positively associated with hr-HPV infection significantly; Education(p=0.0154), was not associated with hr-HPV infection; Number of birth, and candida infection were negatively correlated with hr-HPV infection (p\u0026lt;0.0001).\u003c/p\u003e\n\u003cp\u003eBaseline features of the participants with hr-HPV and TV co-infection are shown in Table 3, primary education, intrauterine contraceptive device as a method of contraception and female with multiple sex partners were more likely to be infected with both TV and hr-HPV.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThough it is recommended to begin primary hrHPV screening at age 25 years in the interim clinical guidance of ASCCP in 2015\u003csup\u003e[18]\u003c/sup\u003e, it raises a number of concerns and questions. When compared to the same strategy starting at 30 years of age, starting at 25 years of age resulted in much higher detection of CIN3+. Still progression to cancer is uncommon, so It is unclear that the identification of these women with CIN3+ would translate into a meaningful reduction of cervical cancer\u003csup\u003e[23]\u003c/sup\u003e. Furthermore, the panel had concerns regarding the potential harms of beginning primary hrHPV screening at age 25 years, particularly with regard to the number of colposcopies, despite the increased detection of disease\u003csup\u003e[24]\u003c/sup\u003e. According to the report \"Global Cancer Statistics 2018\", cervical cancer ranks the fourth in the incidence and mortality of female tumors worldwide, and the second in the rate of female tumors in developing countries \u003csup\u003e[1]\u003c/sup\u003e. HPV infection is a necessary but insufficient condition for cervical cancer \u003csup\u003e[25]\u003c/sup\u003e; the number of cervical cancer patients is far lower than the number of HPV infection female\u003csup\u003e[26]\u003c/sup\u003e. With the development of microbiome, more studies have shown that the composition and changes of the cervical-vaginal microenvironment are closely related to HPV invasion, persistent infection, and the occurrence and development of cervical cancer \u003csup\u003e[27, 28]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn our study, the prevalence of hr-HPV in this region was lower than the hr-HPV prevalence from other parts of China (from 9.03% to 16.8%) \u003csup\u003e[17]\u003c/sup\u003e. The cervical cancer vaccine had not been introduced in China at the time of screening, so all the female had not been vaccinated against HPV yet. This is the first time we have relatively accurate data on hr-HPV infection rates in central China.\u003c/p\u003e\n\u003cp\u003eIt was found that Candida spp was not associated with the detection of cervical lesions in this study, consistent with previous studies \u003csup\u003e[5, 13, 14]\u003c/sup\u003e. Gardnerella vaginalis was not the risk factor of CIN or ICC in our research, either. Gardnerella vaginalis was considered to possess characteristics which are essential for the pathogenesis of BV\u003csup\u003e[6, 29-31]\u003c/sup\u003e, including the production of sialidase \u003csup\u003e[31]\u003c/sup\u003e and vaginolysin, \u003csup\u003e[30, 32]\u003c/sup\u003e. Although some research found that BV played a functional role in female with CIN or ICC\u003csup\u003e[2, 3]\u003c/sup\u003e, the correlation between Gardnerella and the progression of cervical lesions had yet to be described. In this study, Gardnerella has had a low prevalence and was only detected in 1,050 (0.34%) female, and co-infected with Gardnerella didn\u0026rsquo;t increase the risk of CIN or ICC. In the vagina of female without BV, Gardnerella vaginalis was also detected, although it had a lower abundance and prevalence \u003csup\u003e[33, 34]\u003c/sup\u003e. There was enormous substantial genetic diversity within Gardnerella vaginalis\u003csup\u003e[16, 35]\u003c/sup\u003e\u003cem\u003e,\u003c/em\u003e and virulence potential differentiate significantly between various genetic types/clades\u003csup\u003e[15]\u003c/sup\u003e; this may correlate with the result in our study.\u003c/p\u003e\n\u003cp\u003eSeveral pieces of research had concerned the relationship between TV, HPV and CIN/ICC, but their conclusions were inconsistent. Gweneth\u0026rsquo;s study found that trichomonas vaginitis was associated with hr-HPV infection (specifically type 16) significantly, but no correlation between trichomonas and cervical lesions \u003csup\u003e[10]\u003c/sup\u003e. Ishita Ghosh\u0026rsquo;s study found that the higher risk of cervical cancer observed in the female co-infected with HPV and TV was without any enhanced risk of CIN\u003csup\u003e[5]\u003c/sup\u003e. But both of them were small-scale studies. Rui-Mei Feng\u0026rsquo;s pooled analysis found that current TV-positive female had an increased risk for hr-HPV infection compared with currently TV negative female. Both past and current TV-positive female had a decreased risk for CIN 2+\u003csup\u003e[9]\u003c/sup\u003e, but hr-HPV was detected by Hybrid Capture 2 and HPV genotype can\u0026rsquo;t be differentiated, TV was diagnosed by thinprep cytologic test in that research, and this method had a lower detection rate.\u003c/p\u003e\n\u003cp\u003eIn this study, 5,683 among the overall participants were TV positive and 1,952 (34.35%) among these, were co-infected with hr-HPV. Co-infection with TV increased the risk of CIN 1 among female with hr-HPV, and increased the risk of CIN 2-3 among female with HPV 16. It was expected that TV was often associated with more severe inflammatory reaction and HPV persistence, and was likely closely related to the invasion, persistent infection of HPV 16. HPV including hr-HPV infections are mostly temporary. The virus can be cleared through host immune responses spontaneously, only a small number of infections persisted and progressed to cervical cancer \u003csup\u003e[36]\u003c/sup\u003e. HPV 16 was found to be the most prevalent hr-HPV type with the highest risk among all hr-HPVs to progress to CIN2-3 and ICC \u003csup\u003e[37]\u003c/sup\u003e. Studies found that the outcome of HPV infection was closely related to the local micro-environmental of the cervix \u003csup\u003e[27]\u003c/sup\u003e. A lot of research has discovered that TV led to an imbalance of the vaginal flora, which inhibited or reduced the lactobacillus substantially \u003csup\u003e[5]\u003c/sup\u003e, and caused severe inflammation. Evidence were found that the continuous activation of inflammatory transcription factors can lead to cervical tissue damage, and thus improved the susceptibility and carcinogenic ability of HPVl6\u003csup\u003e[10, 38]\u003c/sup\u003e. Meanwhile, the severity of cervical lesions was correlated with the abundance and diversity of cervicovaginal flora positively and correlated with the number of lactobacilli negatively \u003csup\u003e[27, 39]\u003c/sup\u003e. Unlike CIN 1, CIN 2-3 had been considered no longer reversible and required a more definite clinical treatment, the composition and characteristics of the cervical and vaginal flora were very different \u003csup\u003e[40]\u003c/sup\u003e. \u003csup\u003e[2, 3]\u003c/sup\u003e. There may be some complex host immune response to TV and HPV 16 co-infection, but the hypothesis needed further research for validation. There were only 72 ICC in this study, so the correlation between TV, HPV and ICC were inconclusive.\u003c/p\u003e\n\u003cp\u003eBoth TV and genital tract HPV infection are sexually transmitted disease (STD). In the districts with lower economic levels, many people went out to the developed areas to work and couples usually work in different places, and sex act extramarital is common\u003csup\u003e[17]\u003c/sup\u003e. Risk factors including primary education, intrauterine contraceptive device as a method of contraception and female with multiple sex partners significantly increased the odds of hr-HPV and TV co-infection. Compared with female with only one sexual partner, it was found that female with two or more lifetime sex partners had a higher risk of HPV and TV co-infection. Meanwhile, it was found that female who chose intrauterine contraceptive device as a method of contraception had a higher risk of co-infection, as compared with female who chose contraceptive or condom. Female who had primary education also were found to have a higher risk of co-infection compared with higher educated female. As TV is a STD, and it was found that two or more lifetime sex partners and choosing intrauterine contraceptive device instead of condom were associated with co-infection, it was expected that the co-infection is likely closely related to the risky sex behaviors. Sexual interactions with multiple hosts were expected to contribute to the co-infection, because each host may be infected with one kind of special pathogen species \u003csup\u003e[41, 42]\u003c/sup\u003e. The transmission and clinical progression of sexually transmitted infectious diseases may be changed by sexual interactions \u003csup\u003e[43, 44]\u003c/sup\u003e. Risk factors, including the number of pregnancies \u0026ge; 1, post-menopause, poverty, personal HPV history and miscellaneous bacteria density were associated with HPV infection significantly, but they were not related to co-infection significantly.\u003c/p\u003e\n\u003cp\u003eAs it was known that, this research had the largest number of female who received COBAS human papillomavirus primary testing for cervical cancer screening up to now worldwide, and it was a multisite investigation with the most massive scale about the correlation between cervical hr-HPV infection, CIN/ICC and vaginal microenvironment. The detection methods of hr-HPV and vaginal microenvironment in this study were highly sensitive and recognized internationally.\u003c/p\u003e\n\u003cp\u003eOf note, there were some limitations to our study. Because our study was a cross-sectional analysis of current hr-HPV and TV infections, one of its major limitations, which is inherent to the design, is that the association found does not imply causality. It was not clear whether there was a persistent infection among these female or not, so follow-up of TV-infected women to assess whether new CIN detection or CIN stage progression occurs would result in a much more clarifying study to support our findings. Besides, there are some participants who failed to be followed up for a variety of reasons in the screening process. chlamydia has been detected less and less, so it was not included in this study. HIV-infection status and smoking habit has not been included in this study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eFrom this large population-based study, it was found that Positive TV was correlated with hr-HPV infection \u0026nbsp;\u0026nbsp;and co-infection with TV increased the risk of CIN 1 among female infected with hr-HPV, co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16. From what has been discussed above, co-infection of TV and HPV 16 is a significant risk factor for the detection of cervical lesions. For our study was a cross-sectional analysis, there were some limitations, and follow-up of TV-infected women to assess whether new CIN detection or CIN stage progression occurs will be the next step of our work.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received the verification of Medicine Ethics Committee Xiangyang Central Hospital(Approved Code: 2017-004). The project \u0026ldquo;Biological Sample Bank Construction Project of Xiangyang City \u0026lsquo;Two Cancers Screening\u0026rsquo;\u0026rdquo; hosted by Xiangyang Central Hospital involves the collection of samples and related indicators detection of human cervical exfoliated cells and vaginal secretions. The related experiments of this project will strictly abide by ICH-GCP, declaration of Helsinki, International Ethical Guidelines for Biomedical Research Involving Human Subjects. Respect for the right of informed consent of the patient. All the experiments meet routine medical and make protection scheme for patients. All the members of Medicine Ethics Committee approved this project and gave a written consent. Informed consent to participate in this study had been obtained from participants.\u003c/p\u003e\n\u003cp\u003e\u003cbr /\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China(No.81972449). Health Commission Foundation of Hubei, China (No. WJ2019M069); The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDesigned project: XH, LL. Collected samples: QXM, ZM, MXG. Analyzed data: YM, JCF. Generated figures and tables: YM, JCF. Wrote manuscript: YM. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the clinic staff of the hospitals which take part in the cervical cancer screening project in Central China in 2017.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1 Flowchart of screening profile. Among 310545 women, 6067 were tested positive for HPV 16/18, CIN1, CIN2, CIN3, ICC were detected in 480, 265, 346, 75 cases, respectively. 18297 were tested positive for other hr-HPV genotypes, CIN1, CIN2, CIN3, ICC were detected in 381, 112, 77, 2 cases, respectively.\u003c/p\u003e\n\u003cp\u003eFigure 2 Univariate analyses of Candida albicans, Gardnerella, TV for the risk of CIN1/CIN2-3/ICC in different hr-HPV types.\u003c/p\u003e\n\u003cp\u003eFigure 3 Multivariate analysis of hr-HPV infection. Age, highest level of education, number of pregnancies and number of births were set as rank variables. * MBD means miscellaneous bacteria density.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style='font-size: 13px; line-height: 200%; font-family: \"Times New Roman\", serif; color: rgb(0, 0, 0);'\u003eabbreviations\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ethe full name\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ehr-HPV\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ehigh risk HPV\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCIN\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ecervical intraepithelial neoplasia\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eICC\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003einvasive cervical cancer\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTV\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003etrichomonas vaginitis\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eBV\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ebacterial vaginitis\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMBD\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003emiscellaneous bacteria density\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eNILM\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003enegative for intraepithelial lesion or malignancy\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eAGC\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eatypical glandular cells\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSIL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003esquamous intraepithelial lesion\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eLSIL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003elow grade squamous intraepithelial lesion\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eHSIL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ehigh grade squamous intraepithelial lesion\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eASC-US\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eatypical squamous cells of undetermined significance\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eASC-H\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eatypical squamous cells not possible exclude HSIL\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSCC\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003esquamous cell carcinoma\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eECC\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eendocervical curettage\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCIs\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003econfidence intervals\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eother high risk\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:232.45pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSTD\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:232.5pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003esexually transmitted disease\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"References","content":"\u003cp\u003e[1]\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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Sex Transm Dis. 2019. 46(8): 493-501.\u003c/p\u003e\n\u003cp\u003e[43]\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Pedersen AB, Fenton A. Emphasizing the ecology in parasite community ecology. Trends Ecol Evol 2007;22:133-9, doi:http://dx.doi.org/10.1016/j.tree.2006.11.005.\u003c/p\u003e\n\u003cp\u003e[44]\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; Sternberg ED, Lef\u0026egrave;vre T, Rawstern AH, de Roode JC. A virulent parasite can provide protection against a lethal parasitoid. Infect Genet Evol 2011;11:399-406, doi:http://dx.doi.org/10.1016/j.meegid.2010.11.017.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style='font-size: 13px; line-height: 200%; font-family: \"Times New Roman\", serif; color: rgb(0, 0, 0);'\u003eTable 1. Histologic diagnosis distribution in 1952 hr-HPV and TV co-infection population. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 102%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:11.3%;border:none;border-top:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:65.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eHPV genotype\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.42%;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 65.9pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family: \"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.12%;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 65.9pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eNormal\u003csup\u003e#\u003c/sup\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003en (%)\u003c/span\u003e\u003cspan style=\"font-size: 11px; line-height: 200%; font-family: Verdana, sans-serif; background: white;\"\u003e*\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.92%;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 65.9pt;vertical-align: bottom;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCIN1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003en (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.8%;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 65.9pt;vertical-align: bottom;\"\u003e\n \u003cp 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style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e6\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:11.3%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e18\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:17.42%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSingle-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e401(77.12)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e82(15.77)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.8%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e16(3.08)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.66%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e10(1.92)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e11(2.12)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e520\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:17.42%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCo-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e87(82.86)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e13(12.38)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.8%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e3(2.86)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.66%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1(0.95)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1(0.95)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e105\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:11.3%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e18+OHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:17.42%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSingle-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e169(73.48)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e51(22.17)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.8%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e6(2.6)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.66%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e4(1.74)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0(0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e230\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:17.42%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCo-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e15(46.87)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 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style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1(3.13)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0(0)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e32\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:11.3%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:17.42%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eSingle-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e16916(96.95)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e357(2.05)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.8%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e105(0.60)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.66%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e69(0.39)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e2(0.01)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e17449\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:17.42%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCo-infection\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:15.12%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1049(93.83)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.92%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e47(4.20)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:11.8%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e15(1.34)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.66%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e6(0.54)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:10.32%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1(0.09)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:8.38%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:3.25pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e1118\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e#: female who have normal histologic or cytology results. OHR:\u0026nbsp;other high risk type.(\u003c/span\u003e\u003cspan style=\"font-size: 11px; line-height: 200%; font-family: Verdana, sans-serif; background: white;\"\u003e*percentages are calculated in turn; OHR-other high risk.)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;Table 2 Multivariate logistic regression analyses of the risk of CIN1/CIN2-3/ICC by TV stratified by hr-HPV infection status\u003c/span\u003e\u003cspan style=\"font-size: 11px; line-height: 200%; font-family: Verdana, sans-serif; background: white;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:11px;line-height:200%;font-family:\"Verdana\",sans-serif;background:white;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width:99.96%;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.26%;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 31.64%;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003eCIN1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 31.52%;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003eCIN2-3\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 31.52%;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 20.75pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003eICC\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 5.26%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.52%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003en\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.52%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6.58%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003ep\u003c/span\u003e\u003c/em\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.52%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003en\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.52%;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 46.65pt;vertical-align: top;\"\u003e\n \u003cp 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style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:6.46%;border:none;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:5.26%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOHR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003e535\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.73(0.49-1.08)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:6.58%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.1147\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003e344\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.90(0.56-1.45)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:6.46%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.6704\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:center;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height: 200%;font-family:\"Times New Roman\",serif;'\u003e15\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:12.52%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.36(0.12-1.06)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:6.46%;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:42.0pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.0633\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size: 13px; line-height: 200%; font-family: \"Times New Roman\", serif;'\u003eAdjusted for age,\u0026nbsp;\u003c/span\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ethe\u0026nbsp;highest level of education, number of pregnancies, number of births, menopause,\u0026nbsp;miscellaneous\u0026nbsp;bacteria density, poverty,\u0026nbsp;method of contraception, lifetime sex partners, gardnerella\u0026nbsp;and candida spp.\u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size: 11px; line-height: 200%; font-family: Verdana, sans-serif; background: white;\"\u003e\u0026nbsp;(\u003c/span\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOHR-other high risk.\u003c/span\u003e\u003cspan style=\"font-size: 11px; line-height: 200%; font-family: Verdana, sans-serif; background: white;\"\u003e)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eTable 3 Baseline features of the participants with hr-HPV and TV co-infection \u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eOR(95%CI)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid black;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eP\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eeducation\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003ePrimary\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eref\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMiddle and high\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.424(0.377-0.476)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eGraduate\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.540(0.458-0.636)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMarital status\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.1745\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eMarried\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.729(0.462-1.150)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n 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contraception\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;.0001\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eNon-contraception\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.236(0.207-0.270)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eContraceptive\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.335(0.280-0.401)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eCondom\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e0.244(0.208-0.286)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eIntrauterine contraceptive device\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eref\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eLifetime sex partners\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026lt;.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n 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style=\"width: 46.2pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 168.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026ge;2\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003eref\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 46.2pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:10.0pt;margin-left:0in;font-size:15px;font-family:\"Tahoma\",sans-serif;text-align:justify;line-height:200%;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Times New Roman\",serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n 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Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Invasive Cervical Cancer, Cervical Intraepithelial Neoplasia, Human Papillomavirus, Vaginal Microenvironment, Trichomonas Vaginitis ","lastPublishedDoi":"10.21203/rs.3.rs-22259/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-22259/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eEvidence suggested that vaginal microbiome played a functional role in the progression of cervical lesions in female infected by HPV. This study aimed at evaluating the influence of common vaginal infection on the carcinogenicity of high risk HPV (hr-HPV). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eFrom January 15, 2017 to December 31, 2017, 310,545 female aged at least 30 years old had been recruited for cervical cancer screening from 9 clinical research centers in Central China. All the recruited participants received hr-HPV genotyping for cervical cancer screening and vaginal microenvironment test by a high vaginal swab. Colposcopy-directed biopsy was recommended for female who were infected with HPV 16 and HPV 18, and other positive hr-HPV types through test had undertaken triage using liquid-based cytology, cases with the results ≥ ASCUS among them were referred to colposcopy directly, and cervical tissues were taken for pathology examination to make clear the presence or absence of other cervical lesions.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAmong 310,545 female, 6,067 (1.95%) were tested with positive HPV 16 and HPV 18, 18,297 (5.89%) were tested with other positive hr-HPV genotypes, cervical intraepithelial neoplasia (CIN) 1, CIN 2, CIN 3 and invasive cervical cancer (ICC) were detected in 861 cases, 377 cases, 423 cases, and 77 cases, respectively. Candida albicans and Gardnerella were not associated with the detection of cervical lesions. Positive trichomonas vaginitis (TV) was correlated with hr-HPV infection (p\u0026lt;0.0001). Co-infection with\u003cstrong\u003e \u003c/strong\u003eTV increased the risk of CIN 1 among female infected with hr-HPV (OR 1.18, 95% CI: 1.42-2.31). Co-infection with TV increased the risk of CIN 2-3 among female infected with HPV 16 \u0026nbsp;(OR 1.71, 95% CI: 1.16-2.53).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eCo-infection of TV and HPV 16 is a significant factor for the detection of cervical lesions.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Co-infection with trichomonas vaginalis increases the risk of cervical intraepithelial neoplasia grade 2-3 among HPV16 positive female: a large population-based study.","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2020-08-17 14:25:46","doi":"10.21203/rs.3.rs-22259/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-08-14T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-11T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-08-03 18:36:23","doi":"10.21203/rs.3.rs-22259/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-08-10T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-07-27T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-07-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-07-26T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-04-30 16:02:45","doi":"10.21203/rs.3.rs-22259/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-07-14T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-06T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nI wish to thank the Associated Editor for the invitation in this review.\nThe present study was conducted in a large population, consisting of a total of 310,545 women aged at least 30 years old. The female contingent in question underwent screening for the possibility of detecting cervical intraepithelial neoplasms, and their progression to cervical cancer; this operation was performed by 9 clinical research centers in Central China.\nAmong the multitude researches and efforts in the field of hypotheses regarding the very complex process of cervical carcinogenesis, the aim of the study is to provide valuable and statically reliable data towards this direction.\nThe study aims to highlight an important link between hr-HPV infection and mainly HPV 16 and trichomonas vaginitis, thus highlighting the fact that the female vaginal microbiome infected with HPV plays an important (functional) role in the progression of cervical lesions; the study even considers this a contribution to the process of carcinogenesis of women infected with hr-HPV.\nReferring to the methodology, it is clear that the authors have tried rigorously to apply the latest HPV genotyping techniques to identify HPV infection in women as well as to accurately identify the type of HPV, as well as tests to assess vaginal microenvironment. Specifically, the Thinprep cytologic test, the application of the COBAS4800 HPV test which is able to detect infection by 14 types of high-risk HPV (hr-HPV) simultaneously and the individual identification of HPV16 and HPV18, as well as the high vaginal swab that has provided microscopic evaluation of the vaginal microenvironment; thus assessing the presence of Candida albicans, TV, gardnarella and miscellaneous bacteria density.\nAll women infected with HPV 16 and HPV 18 or other types of hr-HPV detected by these tests, as well as all cases of ASCUS detected by liquid-based cytology, underwent cervical biopsy and / or endocervical curettage. Histological diagnoses of cervical lesions are classified as normal, CIN1, CIN2, CIN3, and ICC (cervical cancer).\nThe study is supported by a correct statistical processing, which clearly shows the correlation (between potential risk factors and vaginal pathogen infection) betwen cervical hr-HPV infection, CIN / ICC and vaginal microenvironment. Also the large number of women surveyed makes that this study contributes theoretically to the role of trichomonas vaginitis infection in cervical intraepithelial lesions as well as the possibility of their progression towards ICC.\nI personally believe that the detection methods of hr-HPV and vaginal microenvironment in this study are highly sensitive and internationally recognized. Also, on the other hand, the statistical results of this large population-based study found that Co-infection of TV and HPV 16 poses a high risk for the progression of cervical lesions; in this direction the correlation between cervical hr-HPV infection, CIN / ICC and vaginal microenvirenment is quite clear. Coinfection with TV increased the risk of CIN 1 among female infected with hr-HPV. While Co-infection with TV increased the risk of CIN2-3 among female infected with HPV 16. This statistical result leads to the conclusion that Coinfection of TV and HPV 16 is an important risk for the progression of cervical lesions.\nMinor remarks regarding the study:\nIn the title: I think it is correct that the CIN2-3 abbreviation should be placed in parentheses and replaced with the term cervical intraepithelial neoplasia which explains the fact that it is about the cervix and its neoplastic pre and invasive lesions.\nIn the methods section: All the recruited participants received cervical cancer screening, in my opinion it is necessary to say through hr-HPV genotyping while it is said for vaginal microenvironment test.\nIn the Methods section: triage using liquid-based cytology, cases ……………, to colposcopy directly. When it comes to finding ASCUS, it would be more convenient to talk about the presence or absence of other cervical lesions.\n2.5 Colposcopy-directed biopsy and verification ………… . According to me it would be better to afferm that cervical tissue underwent the preparation of histological sections.\nStatistics: Generally, statistical analysis is correct. I recommend re-formatting the tables, with clearly separated cells from each other, as they contain a lot of information. They should be easy to read.\nUnder Table 1 it should be noted that *percentages are calculated in turn, so as to understand the figure correctly.\nIn Table 2 It is not as clear, how the figures are calculated. e.g. in the IIC group with HPV18, how were calculated the number 12(cases)? The same for the: Group CIN1+HPV 16 (371 cases); Group CIN 1+HPV 18 (149 cases); Group CIN 1 +OHR(535); and for the group CIN2\nAlso, in the explanations made under the Table 2.I suggest adding :OHR-other high risk.\nFigure 3 is more difficult to read. I suggest rotating it by 90 deegres.\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-06-25T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after discretionary revisions\nForm responses:\n---\n\nComments to Author:\n---\nDear Authors\nThe manuscript seems very clear to me, with a very large sample number and a very well-managed approach that shows high-impact results that reinforce others obtained in smaller-scale studies.\nMy comments that could improve the document are the following:\n2. Methods\nLines 55-56\nIn the methods it is defined that the study was carried out in women at least 30 years old, it is suggested that the criterion of why the study did not contemplate women under 30 years old be explained.\n2.5 Colposcopy-directed biopsy and verification of disease status\nLines 98-100\nI suggest describing in more detail the method used for pathological staging or including the reference that supports it.\n4. Discussions\nThe discussions seem complete to me, I only suggest discussing two aspects related to the study population, the age of the women (30 years old and older) and not having been vaccinated against HPV.\nBest regards\nReviewer\n\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please publish my name with my report.**\n"},{"type":"reviewerAgreed","content":"","date":"2020-06-21T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-06-05T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-05-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-04-21T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-04-20T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-04-20T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a5f315a7-f1b5-4dfb-9256-ea3e7e898ac6","owner":[],"postedDate":"August 17th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":309396,"name":"Infectious Diseases"}],"tags":[],"updatedAt":"2020-09-06T15:02:42+00:00","versionOfRecord":{"articleIdentity":"rs-22259","link":"https://doi.org/10.1186/s12879-020-05349-0","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2020-09-01 12:00:00","publishedOnDateReadable":"September 1st, 2020"},"versionCreatedAt":"2020-08-17 14:25:46","video":"","vorDoi":"10.1186/s12879-020-05349-0","vorDoiUrl":"https://doi.org/10.1186/s12879-020-05349-0","workflowStages":[]},"version":"v3","identity":"rs-22259","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-22259","identity":"rs-22259","version":["v3"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}